Cancer is characterized primarily by an increase in the number of abnormal immortal cells derived from a given normal tissue, invasion of adjacent tissues by these abnormal cells, loss of normal cell function and lymphatic or blood-borne spread of malignant cells to regional lymph nodes and to distant sites (metastasis). Clinical data and molecular biological studies indicate that cancer is a multistep process that begins with minor pre-neoplastic changes, which may under certain conditions progress to neoplasia. Neoplastic lesions may evolve clonally and develop an increasing capacity for invasion, growth, metastasis, and heterogeneity, especially under conditions in which the neoplastic cells escape the host's immune surveillance.
There is an enormous variety of cancers that are described in detail in the medical literature. Examples include cancer of the lung, colon, rectum, prostate, breast, brain, skin, blood cells and intestine. The incidence of cancer continues to climb as the general population ages, as new cancers develop, and as susceptible populations (e.g., people infected with AIDS or excessively exposed to sunlight) grow. A tremendous demand therefore exists for new methods and compositions that can be used to treat patients with cancer, to prevent the development of pre-cancerous conditions into cancer and to slow cancer progression.
Current cancer therapies may involve surgery, chemotherapy, hormonal therapy and/or radiation treatment to eradicate neoplastic cells in a patient. More recently, cancer therapies may also involve biological therapy or immunotherapy. All of these approaches pose significant drawbacks for the patient. Surgery, for example, may be contraindicated due to the health of a patient or the location of the tumour. In any case, surgery may not completely remove neoplastic tissue. Radiation therapy is only effective when the neoplastic tissue exhibits a higher sensitivity to radiation than normal tissue. Radiation therapy often elicits serious side effects. Hormonal therapy is rarely given as a single agent. Although hormonal therapy can be effective, it is often used to prevent or delay recurrence of cancer after other treatments have removed the majority of cancer cells. Biological therapies and immunotherapies are limited in number and may produce side effects such as rashes or swellings, flu-like symptoms, including fever, chills and fatigue, digestive tract problems or allergic reactions.
With respect to chemotherapy, there are a variety of chemotherapeutic agents available for treatment of cancer. A majority of cancer chemotherapeutics act by inhibiting DNA synthesis, either directly, or indirectly by inhibiting the biosynthesis of deoxyribonucleotide triphosphate precursors, to prevent DNA replication and concomitant cell division. Despite availability of a variety of chemotherapeutic agents, chemotherapy has serious drawbacks. Almost all chemotherapeutic agents are toxic, and chemotherapy causes significant, and often dangerous, side effects including severe nausea, bone marrow depression, and immunosuppression. Additionally, even with administration of combinations of chemotherapeutic agents, many tumor cells are resistant or develop resistance to chemotherapy. In fact, those cells resistant to the particular chemotherapeutic agents used in the treatment protocol often prove to be resistant to other drugs, even if those agents act by different mechanism from those of the drugs used in the specific treatment. This phenomenon is referred to as pleiotropic drug or multidrug resistance. As a result of drug resistance, many cancers prove refractory to standard chemotherapeutic treatment protocols.
There is a significant and growing need for safe and effective agents and methods for treating, preventing and managing cancer. There is also an increasing need to develop agents and methods that can activate or stimulate an immune response within subjects not only in the context of cancer therapy, but also in response to challenge by other pathogens such as bacteria, viruses, protists, prions, fungi and helminths. This is especially the case in treatment of bacterial infections, in view of the increasing phenomenon of bacterial resistance to antibiotic agents.